Dr Digjaya Utama - Population Health and Immunity division

Dr Digjaya Utama - Population Health and Immunity division

Location: 
Davis Auditorium
Start Time: 
Mon, 17/06/2019 - 3:00pm
End Time: 
Mon, 17/06/2019 - 4:00pm

Host-Parasite Interactions in Plasmodium falciparum Malaria Infection

PhD Completion seminar​

Plasmodium falciparum is the main cause of severe malaria in humans and has been responsible for most malaria-related deaths globally. The development of severe malaria is mainly attributed to sequestration of the infected red blood cells (iRBCs) to the microvascular endothelium, and rosetting of iRBCs with other non-infected RBCs. These mechanisms are mediated by interactions between parasite-encoded variant surface antigens (VSAs) on the iRBCs and host receptors on the endothelial cells and uninfected RBCs, respectively. VSA proteins are encoded by complex multigene families and include PfEMP1, RIFIN and STEVOR. Their differential expression facilitates antigenic variation and cytoadhesion, with some VSA-host receptor interactions associated with severe disease whilst others with only mild or asymptomatic infection. Both host genetic diversity and the level of VSA-specific immunity has been associated with disease severity however they have never been investigated together in natural human and parasite populations. The complexity of between diverse parasites and host environments complicates the effort to understand severe malaria and prevent its manifestation in infected individuals.

During his PhD, Digjaya investigated host genetic polymorphisms in Papua New Guinean children and their association with severe malaria and VSA immunity, the transcriptome of rosetting parasites in different host cell environments, as well as the development of antibody responses against upregulated VSAs. The results showed suggested key elements that link host genetic polymorphisms with differential exposure to malaria antigens. His studies have linked specific combinations of VSA variants to rosetting to both A and O-type RBCs, and potentially, the development of severe malaria. This study highlights the importance of considering both the parasite biology and diverse host environments during P. falciparum malaria infection, which can help guide the development of interventions to reduce the burden of severe malaria.